Frogs vs Bacteria
I’m a big frog fan, but I often have to report bad news about my froggy friends, so it’s great to have some good news about amphibians for a change. By creating “Teflon” versions of natural antibiotic peptides found in frog skin, a research team at the University of Michigan has made the potential drugs better at overcoming bacterial defences.
Compounds called antimicrobial peptides (AMPs) are produced by virtually all animals, from insects to frogs to humans. AMPs are the immune system’s early line of defence, battling microbes at the first places they try to penetrate: skin, mucous membranes and other surfaces. That’s particularly important if you spend your life sitting in a muddy pond. AMPs copiously produced in injured or infected frog skin. In addition to fighting bacteria, AMPs attack viruses, fungi and even cancer cells, so drugs designed to mimic them could have widespread medical applications.
Scientists have been interested in exploiting these natural antibiotics since their discovery in the 1980s, but they have not been able to overcome their practical limitations. In particular, AMPs are easily broken down by proteases secreted by bacteria and which are also naturally present in the human body. Increasing the concentration of AMPs in an effort to get around that problem can cause toxic side effects, such as the destruction of red blood cells. The damage to red blood cells seems to happen because sticky parts of the AMP molecule interact with the cell membrane in a harmful way.
The Michigan team replaced sticky portions of the peptides with non-stick analogs. His inspiration came from the kitchen as much as the chemistry lab: non-stick cookware is coated with fluorinated polymers, plastic-like compounds composed of chains of carbon atoms completely surrounded by fluorine atoms. The fluorine not only makes Teflon slippery, it also makes the coating inert to almost every known chemical. Non-stick, fluorinated AMPs are much more resistant to protease degradation. When treated with purified proteases, the non-fluorinated AMPs were all degraded within 30 minutes. Under the same conditions, the fluorinated AMP was completely intact after 10 hours. This should make them more effective as drugs, as they will persist for longer in the body. The modified peptides were also at least as good at killing bacteria as their non-fluorinated counterparts, and for some bacteria were significantly better. The next stage of the research is to discover whether the fluorinated AMPs are less toxic to red blood cells than their stickier natural equivalents, and if they are, to produce large enough quantities of fluorinated AMPs for clinical trials.
Halogens including fluorine, are highly reactive and they easily form compounds. It therefore becomes tougher for an enzyme to break down these ‘love-locked’ halogenated compounds. The kitchen connection is appropriate in this regard. A nicely presented story. Hopefully, the scientists will change the name from AMP to some other thing, since it clashes with another acronym, Adenosine Mono Phosphate. Regards.
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